Systematic Review and Meta-Analysis Medicine ®

Efficacy of acupuncture for generalized anxiety

disorder
A PRISMA-compliant systematic review and meta-analysis
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Meichen Li, MMa, Xin Liu, MDa, Xinyi Ye, MMb, Lixing Zhuang, MDc,*
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Abstract
Background: Generalized anxiety disorder (GAD) tightly traps modern people. Its incidence shows an increased peak during
the 2019 novel coronavirus (COVID-19) epidemic. Acupuncture is regarded as an effective way to relieve anxiety symptoms.
However, there are still controversies. This study aimed to systematically evaluate the clinical efficacy of acupuncture in patients
with GAD.
Methods: Four English and 3 Chinese databases were searched from their inception to January 2022. Only randomized
controlled trials (RCTs) in which acupuncture was the main intervention were included. The literature was independently screened
and extracted by two investigators. The Cochrane Bias Risk Assessment Tool was used for quality evaluation. Analyses were
conducted by RevMan 5.3.0 and STATA 15.0 software. The primary outcome was the Hamilton Anxiety Scale (HAMA). The
secondary indicators were the total effective rate, the Self-Rating Anxiety Scale (SAS), and the Treatment Emergent Symptom
Scale (TESS).
Results: Twenty-seven studies were included with a total of 1782 participants. The risk of performance bias or reporting bias
for most of the included trials was unclear. Combined results showed the acupuncture group had better outcomes in the HAMA
score [MD = −0.78, 95%CI (−1.09, −0.46)], the total effective rate [RR = 1.14, 95%CI (1.09, 1.19)], the SAS score [MD = −2.55,
95%CI (−3.31, −1.80)] compared with the control group. Regarding the number of adverse events, the acupuncture group was
safer than the control group and scored less grade in the TESS score [MD = −1.54, 95%CI (−1.92, −1.17)].
Conclusions: Acupuncture can effectively relieve the anxiety symptoms of generalized anxiety disorder patients with fewer side
effects, but randomized controlled trials with large sample size and high quality are also required to support the result.
Abbreviations: 5-HT = the serotonin system, AT = acupuncture treatment, CAM = complementary and alternative medicine,
CBM = Chinese Biomedical Literature, CBT = psychotherapy, CI = confidence intervals, CNKI = China Knowledge Network,
COVID-19 = 2019 novel coronavirus, GAD = Generalized anxiety disorder, HAMA = Hamilton Anxiety Scale, MD = mean difference,
PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses, RCTs = randomized controlled trials, RR =
relative risk, SAS = the Self-Rating Anxiety Scale, TER = Total effective rate, TESS = Treatment-Emergent Symptom Scale, VIP =
China Science and Technology Journal, WF = Wanfang, .
Keywords: acupuncture, generalized anxiety disorder, meta-analysis, randomized controlled trial, systematic review

1. Introduction 5–7% among the population.[1,2] It occurs especially frequently

in women.[3] During menopause, the occurrence is as high as
Generalized Anxiety Disorder (GAD) is a major subtype of 63.3%.[4] Besides, the incidence shows an increased peak during
common chronic anxiety disorder, with a total incidence of the 2019 novel coronavirus (COVID-19) epidemic.[5–7] GAD

This work was supported by the National Natural Science Foundation of a

China (81903971), and the Natural Science Foundation of Guangdong
Province (2021A1515011470). Innovative Clinical Research Project of
the First Affiliated Hospital of Guangzhou University of Chinese Medicine
(2019ZWB07).
All authors have completed the ICMJE uniform disclosure form (available at http://
dx.doi.org/10.21037/apm-21-499). The authors have no conflicts of interest to
declare.
The authors are accountable for all aspects of the work in ensuring that questions
related to the accuracy or integrity of any part of the work are appropriately
investigated and resolved.
Ethical approval: Since our research did not have close or direct contact with
every patient, no ethical clearance was required for this manuscript.
The datasets generated during and/or analyzed during the current study are
available from the corresponding author on reasonable request.
Acupuncture and rehabilitation clinical collage of Guangzhou University of
Chinese Medicine, b Dongguan Traditional Chinese Medicine Hospital, c The First
Affiliated Hospital of Guangzhou University of Chinese Medicine.
*Correspondence: Lixing Zhuang, The First Affiliated Hospital of Guangzhou
University of Chinese Medicine, Guangzhou, China (e-mail: zhuanglixing@163.com).
Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open-access article distributed under the terms of the Creative
Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is
permissible to download, share, remix, transform, and buildup the work provided
it is properly cited. The work cannot be used commercially without permission
from the journal.
How to cite this article: Li M, Liu X, Ye X, Zhuang L. Efficacy of acupuncture for
generalized anxiety disorder: A PRISMA-compliant systematic review and meta-
analysis. Medicine 2022;101:49(e30076).
Received: 20 April 2022 / Received in final form: 25 June 2022 / Accepted: 28
June 2022
http://dx.doi.org/10.1097/MD.0000000000030076

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 Li et al. • Medicine (2022) 101:49Medicine
mainly manifests as persistent, uncontrollable, and excessive anx-
iety. Physical symptoms trouble patients seriously, such as sleep
disturbance and muscle tension.[8–10] The discomfort is especially
acute during the outbreak, which is easily combined with other
mental disorders and develops into bipolar disorder.[11]
Modern medical research believes that the serotonin system
(5-HT) is of great importance to fear and anxiety.[12] Selective
serotonin reuptake inhibitors are focused on solving the prob-
lem of GAD,[13] such as benzodiazepines. However, the use
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of these neurological drugs has been questioned due to their
adverse effects on the public and physical dependence.[14] It is
increasingly urgent to find effective treatments for GAD.
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At present, patients are gradually opting to combine medica-
tions with complementary and alternative medicine (CAM) treat-
ments to reduce anxiety symptoms.[15,16] Acupuncture therapy is
targeted, flexible, effective and safe, which has been practiced as
an adjuvant treatment for GAD in plenty of clinical trials.[17,18]
However, most of them are randomized controlled trials (RCTs)
with small sample sizes and single centers. There are still contro-
versies about the scientific basis and safety assurance. Therefore,
Figure 1. Search Flowchart.
2
this study aims to collect clinical RCTs of acupuncture in the treat-
ment of GAD and conduct a meta-analysis of the included litera-
ture, to provide an evidence-based basis for clinicians.
2. Materials and methods
2.1. Study registering and reporting
This is a systematic review, and ethical approval was not necessary.
The protocol of this review was registered on PROSPERO (https://
www.crd.york. ac. uk/PROSPERO/; trial ID CRD42020205834).
The following list was provided based on Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA)
(available at http://dx.doi.org/10.21037/apm-21-499).[19]
2.2. Literature inclusion and exclusion criteria
Literature was included if the following criteria were met:
(a) Research type and design: clinical RCTs of acupuncture
treatment (AT) for GAD published at home and abroad;
 Li et al. • Medicine (2022) 101:49www.md-journal.com

(b) Research objects: met the GAD diagnostic criteria; (c)
Intervention measures: the experimental group adopts only
AT (needle materials, acupoint selection, needle implemen-
tation, needle retention time and course were not limited) or
combined with the conventional treatments (psychotherapy or
western medicine). The intervention measures of the control
group were western medicine (the type of medicine was not
limited), psychotherapy (CBT), or western medicine plus CBT;
(d) Clinical efficacy outcome indicators: primary indicators:
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gov) and the Chinese Clinical Trials Registry (www.chictr.org.
cn/searchproj.asp), to screen the completed but unpublished
clinical studies to find as many relevant studies as possible.
Subject and free words were combined for document retrieval.
The search term of the disease was “generalized anxiety disor-
der”; the intervention measures were “acupuncture treatment”
or “acupuncture” or “acupuncture therapy”. The retrieval date
was up to 2022-01. The search strategy of PubMed is as follows:

the Hamilton Anxiety Scale (HAMA); secondary indicators: #1 Search ((“Generalized Anxiety Disorder” or “Disorder,
the Self-Rating Anxiety Scale (SAS), the Total Effective Rate Anxiety” or “Anxiety Disorders”)).
(TER) and the Treatment Emergent Symptom Scale (TESS). #2 Search (“Acupuncture” [Mesh]) OR ((“Acupuncture
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Literature was excluded if one of the following criteria were
met: (I) Non-RCT test or self-control RCTs; (II) Comparison of
curative effects of different acupuncture techniques, acupoint
selection and treatment time, etc; (III) The control group did
not belong to western medicine or CBT; (IV) There were obvi-
ous quality problems in the literature, such as statistical errors;
(V) Documents with incomplete research data or original data
could not be obtained; (VI) Literature review, evaluation lit-
erature, theoretical research, case report, clinical experience,
academic theoretical discussion, repetitive literature, etc.
2.3. Methods of obtaining literature
A comprehensive search of the electronic databases was con-
ducted including the Chinese Biomedical Literature (CBM
http://www.sinomed.ac.cn/), China Knowledge Network (CNKI
https://www.cnki.net/), China Science and Technology Journal
(VIP http://www.cqvip.com/), Wanfang (WF http://www.wan-
fangdata.com.cn), PubMed, Embase and Cochrane Library
databases. Relevant references. Master’s and doctoral degrees
papers were also selected. In addition, we searched the National
Institutes of Health Clinical Trials Database (http://clinicaltrials.
treatment” or “Electroacupuncture” or “Acupuncture, Ear”
or “Acupuncture Points”)).
#3 #1 AND #2.
2.4. Data extraction and management
After the literature was downloaded, the search results were
imported into the Note- Express3.60 document management
software to filter out the duplicate documents. Then, the title and
abstract were read to conduct a preliminary screening. The articles
that passed the first checkpoint were further sieved in full text.
Finally, an excel table was developed according to the relevant
information items to extract data and analyze the results. All doc-
uments were independently screened by two people (M Li and X
Ye) and cross-checked with each other. In case of disagreement,
they would discuss and resolve it with the third researcher (X Liu).
2.5. Literature quality evaluation
According to Cochrane Handbook 5.1.0,[20] the included RCTs
were evaluated by the quality and risk of bias, rated as low-risk,

Table 1
Basic characteristics of the included literature.
Treatment measures
Included literature Sample size Therapy Control Outcome Course

WANG 2003(10) 30/32 EA WM (Trazodone Hydrochloride) ①②③ 6 weeks

WANG 2005(11) 35/30 AT WM (lorazepam & oryzanol/ propranolol) ②③ A month
LIU 2007(1)(12) 29/29 AT WM (Paroxetine) ①②③④ 6 weeks
LIU 2007(2)(12) 28/29 AT + WM WM (Paroxetine) ①②③④ 6 weeks
WANG 2007(13) 21/20 AT WM (Flupentixol and Melitracen) ①③ A month
FU 2008(1)(14) 20/20 AT WM (Paroxetine) ①②③④ 6 weeks
FU 2008(2)(14) 20/20 AT + WM WM (Paroxetine) ①②③④ 6 weeks
DENG 2009(15) 28/27 AT + WM WM (Flupentixol and Melitracen) ①③④ A month
TAI 2010(1)(16) 23/21 AT + CBT CBT ②③ 4–8weeks
TAI 2010(2)(16) 29/21 AT + CBT CBT ②③ 4–8 weeks
SHI 2010(17) 30/30 AT WM (Flupentixol and Melitracen) ①②③④ 4 weeks
GONG 2012(18) 56/57 AT + CBT WM (Duloxetine) ①③④ 6 weeks
XIONG 2013(19) 36/35 AT WM (Flupentixol and Melitracen) ②③ A month
ZHOU 2013(20) 40/40 AT WM (clonazepam) ① 6 weeks
ZHAO 2014(21) 30/30 AT WM (Paroxetine) ①②③④ 6 weeks
FANG 2014(22) 50/50 AT + CBT CBT ① 4 weeks
FAN 2014(23) 40/41 EA + AT WM (Paroxetine) ① 6 weeks
CHE 2015(24) 40/40 AT WM (Paroxetine) ①②④ 6 weeks
SHENG2015(1)(25) 30/30 AT WM (Paroxetine) ③ 6 weeks
SHENG 2015(2)(25) 30/30 AT WM (Paroxetine) ③ 6 weeks
LI 2015(26) 21/24 AT WM (Paroxetine) ① 6 weeks
ZHOU 2015(27) 30/30 AT + WM WM (Paroxetine) ① 8 weeks
XU 2016(28) 30/30 AT + WM WM (Buspirone hydrochloride) ①③ 15 days
ZHANG 2018(29) 48/42 AT + CBT CBT ① 28 days
ZHAO 2018(30) 60/60 EA WM (Buspirone hydrochloride) ①③ 6 weeks
LIANG 2020(1)(31) 38/38 AT WM (Paroxetine) ①②③④ 4 weeks
LIANG 2020(2)(31) 38/38 AT WM (Paroxetine) ①②③④ 4 weeks
Note: ①HAMA: the Hamilton Depression Rating Scale ②SAS: the Self-Rating Anxiety Scale ③TEF: the Total Effective Rate ④TESS: Treatment Emergent Symptom Scale.
AT = Acupuncture treatment, EA = Electro-acupuncture, WM = Western Medicine.

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Table 2
Bias evaluation results of included literature.
Included Random sequence Allocation Blind researchers Blind Completeness Selective Other
literature generation hiding or subjects Evaluator of outcome report biases

WANG 2003[9] L U U U L U U
WANG 2005[10] U U U U L U U
LIU 2007(1)[11] L L U U L U U
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LIU 2007(2)[11] L L U U L U U
WANG 2007[12] H U U U L U U
FU 2008(1)[13] L L U U L U U
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FU 2008(2)[13] L L U U L U U
DENG 2009[14] L U U U L U U
TAI 2010(1)[15] U U U U L U U
TAI 2010(2)[15] U U U U L U U
SHI 2010[16] H U U U L U U
GONG 2012[17] U U U U L U U
XIONG 2013[18] U U U U L U U
ZHOU 2013[19] H U U U L U U
ZHAO 2014[20] L U U U L U U
FANG 2014[21] L U U L L U U
FAN 2014[22] L U U L L U U
CHE 2015[23] U U U U L U U
SHENG 2015(1)[24] L U U U L U U
SHENG 2015(2)[24] L U U U L U U
LI 2015[25] U U U U L U U
ZHOU 2015[26] U U U U L U U
XU 2016[27] L U U U L U U
ZHANG 2018[28] H U U U L U U
ZHAO 2018[29] L U U U L U U
LIANG 2020(1)[30] L L U L L U U
LIANG 2020 (2)[30] L L U L L U U
Note: L = low risk, U = unclear risk, H = high risk.

unclear, or high-risk level. The evaluation basis is mainly as 3. Results

follows: (I) Whether the random method is appropriate; (II)
Whether there is allocation concealment; (III) Whether the blind
method is implemented; (IV)Whether the result data is com-
plete; (V)Whether there is selective reporting of results; (VI)
Whether there are other biases. The quality evaluation process
of the included studies was cross-checked by two evaluators (M
Li and X Ye). For included articles that were divergent and dif-
ficult to determine, the two parties would negotiate or the third
evaluator (X Liu) would help to decide a solution.
3.1. Literature search results
398 literatures were initially excavated through seven major
databases, containing 270 in Chinese and 128 in English. 22
articles were finally included in the study, involving 900 cases
in the treatment group and 882 cases in the control group. The
literature retrieval process was shown in Fig. 1 and the basic
characteristics of the included studies were on record in Table 1.
3.2. Features of included studies

2.6. Statistical methods
Revman 5.3.0 (Cochrane Collaboration, Copenhagen,
Denmark) and STATA 15.0 software (StataCorp, College
Station, TX) were used for meta-analysis. The HAMA score,
the SAS score, and the TESS score were both continuous vari-
ables, and the mean difference (MD) was estimated. TER was
a categorical variable and the relative risk (RR) was selected.
The effect sizes were expressed in 95% confidence intervals
(95% CI). The heterogeneity between studies was tested by I²
or Q. If I2 < 50%, P > .05, it means that there was no statistical
heterogeneity among the studies, and the fixed effects model
was used to combine the effect values; If I2 > 50%, P < .05,
it meant that the heterogeneity between the studies could not
be ignored. For that one-by-one elimination was conducted
to find the possible sources of the heterogeneity (clinical het-
erogeneity or methodological heterogeneity), and sensitivity
analysis was applicated to test the robustness of the results. If
the heterogeneity could not be eliminated, the random-effects
model would finally analyze the effect value. Besides, Revman
5.3.0 was used for inverted funnel chart qualitative analysis,
and STATA 15.0 software was applied for Egger test quantita-
tive analysis for publication bias detection.
3.2.1. Research type. A Parallel randomized control design
was adopted. Five included articles are academic papers,[21–25] and
17 pieces are journaled papers. Five 3-arm experiments[21,25–28]
were divided into double-arm experiments for statistics. Finally,
a total of 27 databases were reviewed. And all studies reported
baseline similarity of patients before treatment.
3.2.2. Intervention measures. In the intervention group, 17
trials used acupuncture alone, 7 trials used the combination
of acupuncture and western medicine, and 3 trials used
the combination of acupuncture and CBT. In the control
group, 23 articles compared acupuncture with western
medicine (paroxetine, Flupentixol and Melitracen, Trazodone
Hydrochloride, buspirone hydrochloride, lorazepam &
oryzanol/ propranolol, lorazepam, duloxetine, clonazepam).
Four studies compared acupuncture with CBT.
3.2.3. Measurement indicators. The primary outcome was
the HAMA score. The secondary indicators were the TER, SAS
score, and TESS score. The HAMA score reduction rate was
recorded in 21 documents. The TER was selected in 25 articles.
The SAS score was scored in 14 articles. The TESS score was
recorded in 11 documents.

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Figure 2. HAMA Forest plot.

3.3. Evaluation of the quality of included studies assessors (14.81%); 11 (40.74%) mentioned withdrawal;
15 literatures clarified the specific random method Loss to follow-up bias and reporting bias was well con-
(55.56%); 6 documents adopted the envelope method trolled in the all of the included research. The details are
for distribution hiding (22.22%); 4 articles blinded the exhibited in Table 2.

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Figure 3. The Total Effect Rate Forest plot.

3.4. Meta-analysis found as a suspicious influencing factor. After the article of Che
Lina was removed, the heterogeneity decreased (I2 < 50%), and
3.4.1. The HAMA score. A total of 21 articles were
[21–26,29–40]
the fixed effects model was finally applied to analyze the final
included to evaluate the remission of the HAMA score. The
results. Results of subgroup analyses indicated that acupunc-
heterogeneity among the studies was statistically significant
ture appeared an anxiety improvement compared with paroxe-
(I2 = 71%, P < .00001), and a random-effects model was
tine [MD = –1.16, 95%CI (–1.96, –0.36)] and Flupentixol and
selected. The results showed that the HAMA score of AT group
Melitracen [MD = –1.72, 95%CI (–3.21, –0.24)]. The results
was lower than the control group, and the difference was
were shown in Fig. 2. The funnel chart and Egger test were per-
statistically significant [MD = –1.26, 95%CI (–1.96, –0.56)].
formed by STATA 15.0 software. The results suggest that there
One-by-one elimination and sensitivity analysis were per- was no publication bias [t = –0.82, 95% CI (–2.11), –0.92),
formed to consider the large heterogeneity, and Che Lina was P > .05], and the credibility of the included literature was high.

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Figure 4. The total Effect Rate Funnel plot.
3.4.2. The Total effective rate. A total of 25 articles[21–31,33,34,36–42]
were included to estimate the remission rate of the HAMA
score. The heterogeneity among the studies was not statistically
significant (I2 = 27%, P > .05), and the fixed effects model
was conducted. Results of subgroup analyses indicated that
acupuncture appeared an active effect on the anxiety symptom
compared with paroxetine [RR = 1.18, 95%CI (1.10, 1.28)] and
Flupentixol and Melitracen [RR = 1.10, 95%CI (1.01, 1.20)].
The result was shown in Fig. 3. The funnel chart (Fig. 4) and
Egger test suggest no publication bias [t = 4.12, 95 % CI (0.90,
2.71), P = .00].
3.4.3. The SAS Score. A total of 14 articles[21,23,25–27,29,33,36,41,42]
reported SAS score. The heterogeneity among the studies was
statistically significant (I2 = 72%, P < .0001), So the random-
effects model was selected. The results showed the difference
in clinical efficacy between the AT group with the control
group was statistically significant [MD = –3.19, 95%CI (–4.78,
–1.61)].
By excluding the literature one by one and sensitivity anal-
ysis to find the source of heterogeneity, Che Lina was thought
of as a suspicious influencing factor. After the article exclusion,
the heterogeneity decreased (I2 < 50%), and the final analysis of
the data results adopted the fixed-effects model. Results of sub-
group analyses indicated a statistically significant difference that
acupuncture performs a positive effect on the anxiety symptom
compared with paroxetine [MD = –1.98, 95%CI (–2.87, –1.09)]
and Flupentixol and Melitracen [MD = –4.39, 95%CI (–7.42,
7
–1.35)]. The result was shown in Fig. 5. The funnel chart and
Egger test suggested no publication bias, and the credibility of
the included literature was high [t = 0.07, 95% CI (–2.07, 2.20),
P = .95].
3.4.4. The TESS score. A total of 11 articles[21–23,25,26,31,33,36]
applied TESS score. The heterogeneity among the studies was
statistically significant (I2 = 78%, P < .0001), so a randomized
effect model was conducted. The results revealed that few
adverse events occurred in the acupuncture group compared
with the control group and the difference was statistically
significant [MD = –1.99, 95%CI (–2.72, –1.27)].
Then one-by-one elimination and sensitivity analysis were
carried out to find the heterogeneous sources, Che Lina seemed
like a suspicious influencing factor. After the article was
removed, the heterogeneity decreased (I2 < 50%), and the anal-
ysis was finally analyzed by the fixed-effects model. The results
delineated that AT group reported fewer adverse reactions. The
final result was shown in Fig. 6. Funnel chart and Egger test con-
firmed the reliability of the included literature [t = 0.71, 95% CI
(–2.90, 5.39), P > .05].
4. Discussion
Over the past 2 years, COVID-19 has spread around the world
and infected millions of people.[43] The pandemic has changed
our way of life and threatened our health. In addition to caus-
ing physical health problems globally, the outbreak has also made
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Figure 5. SAS Forest plot.
a major impact on our mental health. Wearing masks, isolation,
and protection has greatly reduced the way we relieve stress.[44]
On the contrary, pressure sources such as online check-in, online
classes, grabbing shopping resources, unemployment, car loans,
and mortgages have skyrocketed,[45] which leads to unending anx-
iety, depressive symptoms, insomnia, panic, and denial. It belongs
to one of the important reasons for the rapid increase in the prev-
alence of GAD during the epidemic. Huang Y et al conducted a
cross-sectional online survey among Chinese citizens aged ≥18
years from January 31 to February 2, 2020. The study surveyed
4827 participants across 31 provinces and autonomous regions
in mainland China. The online survey showed the prevalence of
GAD was up to 22.6% across the 31 areas, and the highest preva-
lence was up to 35.4% in the Hubei province.[46] It may be benefi-
cial to promote public mental health by enhancing stress resistance
during the COVID-19 outbreak, and it is helpful to buffer the neg-
ative psychological impact of fears about the novel coronavirus.[47]
Acupuncture treatment for GAD is still controversial. To obtain
reliable clinical evidence, this study design a reasonable retrieval
strategy to fully obtain associated literature for meta-analysis.
Based on the specification of clinical guidelines,[13] the HAMA
scores from 14 to 28 are regarded as mild to moderate degrees of
anxiety, and CBT is recommended. The HAMA scores from 28 to
56 belong to the scope of severe anxiety, and anti-anxiety medi-
cine is the main treatment means. Therefore, we define the inter-
ventions of the control group to be Western medicine or CBT.
8
A total of 1782 patients, originating from the clinic or inpa-
tient department of the hospital, were included. Among the
included articles, few of them mentioned anxiety levels. 24
pieces employed western medicine as a positive control and
only 4 chose CBT instead. The results seemed to indicate the
bottleneck of GAD treatment. Due to the professionalism
and specificity of CBT,[9] western pills were irregularly used
instead. It reminded us that GAD needs to be further strength-
ened in the guideline diagnosis of grading to better standard
treatment.
The literature was classified by different western medicine
and the CBT for subgroup analysis, and we incorporated mul-
tiple ending indicators to ensure the accuracy and reliability
of the research. In the HAMA scores and TER, acupuncture
showed better efficacy for GAD compared with Paroxetine,
CBT, Flupentixol and Melitracen. Besides, acupuncture reported
fewer side effects. However, high integrated heterogeneity was
found. After one-by-one elimination and sensitivity analysis,
the article of Che Lina was found to affect heterogeneity. The
possible reasons for the production of heterogeneity are as fol-
lows: (1) Methodology of the literature is incorporated, which
makes it unable to follow the whole trial principles during clin-
ical treatment. (2) The process of generating a random sequence
is not explicitly reported and without hidden and blinding. (3)
The amount of test samples is too small and the data quality is
uneven.
 Li et al. • Medicine (2022) 101:49www.md-journal.com
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wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/02/2023
Figure 6. TESS Forest plot.
Given that this study only observes the efficacy, without
exploring the effects of different intervention methods, such
as acupuncture (acupuncture course, duration, etc.) or changes
in parameters of western medicine (western medicine Dosage,
etc.), a large number of high-quality RCTs are still needed to
further verify the effectiveness and safety of acupuncture for
GAD.[48]
GAD patients still lack understanding and acceptance of
CBT,[49] which may be related to the current lack of psycho-
logical counselors in China[50] and the chaos of the psycho-
logical counseling clinics.[51] Besides, given the long-term side
effects, patients often refuse to insist on taking western med-
icine. Acupuncture is gradually becoming an alternative to
relieve anxiety disorders during the epidemic. However, due to
the small sample size of the included literature, it is not clear
that there is a significant association between acupuncture and
GAD. Researchers are encouraged to design future experiments,
including larger sample sizes and more rigorous experimental
designs.
5. Conclusion
In summary, the results of this study suggest that acupuncture
has clear superiority in relieving anxiety symptoms compared
with western medications or psychotherapy, so acupuncture is
recommended for improving the quality of health for patients
with generalized anxiety disorder during COVID-19. It is hoped
that this research can play a certain role in replenishing the defi-
ciencies of psychotherapy and improving the standard use of
anti-anxiety drugs. It also provides references for clinicians to
make superior decisions. However, high-quality clinical trials
will be needed in the future.
Author contributions
(I) Conception and design: M Li; (II) Administrative support:
L Zhuang; (III) Provision of study materials or patients: X Liu;
(IV) Collection and assembly of data: M Li, X Ye; (V) Data
9
analysis and interpretation: M Li, X Liu; (VI) Manuscript writ-
ing: All authors; (VII) Final approval of manuscript: All authors.
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